Process of making a resorbable implantation device

ABSTRACT

Resorbable materials and their preparation based on gelling a solution of a single polylactide enantiomer. The gel may be dried to produce solid materials, or may be extracted with a nonsolvent prior to drying to make microporous materials. Physical and mechanical properties of the material may be varied by varying the molecular weight of the gelling polymer, or by blending the gelling solution with other polymers or fillers. The resorbable materials can be used to make biodegradable implantation devices.

This is a continuation of application Ser. No. 07/528,968, filed May 24,1990now abandoned, which was a continuation-in-part of application Ser.No. 07/489,078, filed Mar. 5, 1990 and now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to resorbable materials made by gelling asolution of a single polylactide enantiomer. Such materials can be usedto make resorbable implantation devices of designed morphology andthickness.

2. Description of Related Art

The poly alpha-hydroxy acids are a class of synthetic aliphaticpolyesters, the main polymers of which are polylactide (alternativelyreferred to as polylactic acid) and polyglycolide (alternativelyreferred to as polyglycolic acid). These materials have beeninvestigated for use in a variety of implant systems for soft tissue andosseous repair in medicine and dentistry, since they tend to exhibitvery good biocompatibility and are biodegradable in vivo. The need toremove the device after tissue repair can thereby be reduced oreliminated. The alpha-hydroxy acids are also being investigated forproduction of controlled release rate delivery systems for bioactivematerials, such as pharmaceuticals.

The repair of osseous defects, such as developmental malformations andsurgical resections, has stimulated development and application of awide range of synthetic and natural bone repair materials or bonesubstitutes. Iliac crest autograft has been shown to be an effectivegraft material (See, for example, Goldstrohm et al., J. Trauma,24:50-58, 1984), but the supply is limited, requiring, in some cases ofsegmental defect repair or tumor resorption, multiple procedures toobtain sufficient material. In addition, the removal of cancellous graftcan create additional surgical trauma, increase the potential forinfection, and, by lengthening the operating time, increase the risk.

These disadvantages have spurred investigations of alternative bonerepair materials. Bioceramics of calcium phosphate have attractedwidespread attention because of their biocompatibility and chemicalsimilarity to the bone matrix, which results in direct bonding to bonewithout intervening fibrous tissue (See, Osborn et al., Biomaterials,Winter, Gibbons, Plenk (eds.), 1980). However, they tend to be brittle,difficult to shape, and remain in the repair for time periods greaterthan 12 months (See, Holmes et al., Clin. Orthop. Rel. Res., 188:252-62,1984).

The ability to vary the biodegradation rate of syntheticalpha-polyesters by material selection, copolymerization, control ofmolecular weight, crystallinity and morphology makes them attractive forbone repair. Resorption rate can be varied from two weeks to over ayear, for example, so that implant resorption may be tuned to bonerepair rates (See, Hollinger et al., Clin. Orthop. Rel. Res.,207:290-305, 1986). PLA/PGA copolymers have been used alone (Hollinger,J. Biomed. Mater. Res., 17:71-82, 1983) and as binders for bioceramics(Higashi et al., Biomaterials, 7:83-87, 1986) and decalcified allogeneicbone (Schmitz et al., Clin. Orthop. Rel. Res., 237:245-55, 1988) toproduce bone fillers for repairing bony deficiencies in animals.

Such polymers can also function as delivery systems for growth factor(s)as they tend to biodegrade. U.S. Pat. No. 4,578,384 discloses aprotein-acidic phospholipid addition to PLA/PGA copolymer which isreported to increase bone healing rates in rat tibias relative to thecopolymer. PLA could, in itself, play a dual role of bone filler andbone growth factor. Hollinger, J. Biomed. Mater. Res., 17:71-82 (1983),reported that a 50:50 copolymer of poly(L-lactide co-glycolide)increased the rate of early osseous healing when implanted in rat tibialdefects. Thus, it appears that the degradation products of these linearaliphatic polyesters may play a role in the stimulation of hard and softtissue growth, which increases the attraction of using PLA and PGA forrepairing soft or hard tissue.

Metal internal fracture fixation plates, produced for example fromstainless steel, frequently have an elastic modulus greater than tentimes that of bone. Although plate rigidity is an advantage forachieving primary osseous union, it tends to inhibit external callusformation, which is considered a good method for restoring the strengthof the broken bone to its original level (See, Kelley et al., Advancesin Biomedical Polymers, Gebelein, C. G. (ed.), Plenum Press:New York,1987). Active remodeling of the bone after fracture healing may also becompromised unless the rigid plate is removed, often resulting in stressprotection and, consequently, osteoporosis and atrophy beneath theplate.

The potential advantages of internal fixation devices produced frombiodegradable polymers have long been recognized. Primary bony union andcallus formation could be achieved by an adequately stiff and strongplate. Load transfer to the healing bone and bone remodeling may bepromoted by a gradually reducing plate stiffness as biodegradationproceeds. Finally, the need for plate removal may be eliminated byresorption of the device.

Kulkarni et al., Arch. Surg., 93:839-43 (1966), describe the productionof poly(DL-lactic acid) pins for reduction of mandibular fractures indogs. Getter et al., J Oral Surg., 30:344-48 (1972), describe the use ofhigh molecular weight PLA plates to treat mandibular fractures in dogs.Leenslag et al., Biomaterials, 8:70-73 (1987), disclose treatment offractured zygoma in 10 patients using high molecular weight PLA plates.Such polymers, however, tend to be absorbed very slowly. Bostman et al.,J. Bone and Joint Surgery, 69-B. No. 4 (1987), describe the use of highstrength, fast resorbing, self-reinforced PLA/PGA rods for routinetreatment of patients with displaced malleolar fractures.

Soft tissue repair has been a major area of application for syntheticbiodegradable polymers. Reul, Ann J. Surg., 134:297-99 (1977), describesthe use of "Vicryl" (Polyglactin 910) sutures in general surgical andcardiothoracic procedures. Absorbable meshes are often used to perform abuttressing role for soft tissue during healing, and may also act as ascaffolding system for ingrowth of connective tissue. Greisler, Arch.Surg., 117:1425-31 (1982), describes vascular grafts produced frombi-component fabrics based on Dacron and biodegradable polyester fibers.These are reported to achieve the required low bleeding porosity atimplantation and high porosity during the healing stage as degradationproceeds. Tissue regeneration is promoted by tissue growth and adherenceto the biodegradable scaffold provided by the graft structure.

The lactide/glycolide polymers and copolymers tend to demonstrate aneasily characterized and controllable degradation rate and tend to benontoxic, which is advantageous for manufacture of controlled releaserate delivery systems for a wide variety of bioactive materials, such aspharmaceuticals. U.S. Pat. No. 4,563,489 discloses production of abiodegradable polymer delivery system for bone morphogenetic proteinbased on a poly (lactide co-glycolide) copolymer. Development ofsuitable delivery methods is important for such therapeutic proteinssince they are readily absorbed by the body. Schakenraad et al.,Biomaterials, 9:116-20 (1988), describe the development of abiodegradable hollow fiber of poly(L-lactide) for controlled release ofcontraceptive hormone.

U.S. Pat. No. 4,719,246 discloses compositions wherein segments of poly(R-lactide) interlock or interact with segments of poly (S-lactide),producing a crystalline phase having a melting point higher than that ofeither component. Processes are described for preparing the abovecompositions, e.g., by mixing and combining the previously preparedpolymeric components in a suitable solvent or in the molten state andprocesses for preparing gels and porous structures of the compositions.The patent discloses spontaneous gel formation from solutions of blendedpolylactide enantiomers on stirring. It is described that porousstructures are produced from gels of the composition by a processcomprising solvent exchange and evaporation.

U.S. Pat. No. 4,637,931 discloses production of a bone repair materialconsisting of decalcified freeze-dried bone (DFDB) and biodegradablebiocompatible copolymer, namely poly[L(-) lactide co-glycolide]copolymer, which is described as being used for improving andaccelerating the healing of osseous tissue.

U.S. Pat. No. 4,578,384 discloses a material, consisting of acombination of a proteolipid and a biodegradable, biocompatiblecopolymer which is stated to facilitate improved healing of osseouswounds when implanted at the site of the broken tissue.

The methods disclosed in Pat. Nos. 4,637,931 and 4,578,384 for producingbiodegradable bone repair materials from polymer solutions generallycomprise the stages of polymer dissolution, polymer precipitation in anonsolvent, partial drying of the precipitate and compaction of wetprecipitate in a mold, followed by heating/drying to produce thefinished implant.

U.S. Pat. No. 4,563,489 discloses a biodegradable PLA polymer deliverysystem for bone morphogenetic protein (BMP) to induce formation of newbone in viable tissue. The delivery composition described issubstantially pure BMP in combination with a biodegradable PLA polymer,prepared by admixing the BMP with the biodegradable polymer. Thecomposition is implanted in viable tissue where the BMP is slowlyreleased and induces formation of new bone.

The method for preparing the implant material of U.S. Pat. No. 4,563,489generally comprises (1) dissolving the physiologically acceptablebiodegradable polymer in a solvent such as ethanol, acetone orchloroform, (2) admixing the polymer solution with BMP to form adispersion of BMP in the polymer solution and (3) precipitating thecomposite by adding a second solvent which causes precipitation of thepolymer or lyophilizing the dispersion or otherwise treating thedispersion to remove it from solvent and form the BMP-PL composite.After composite formation, it is filtered, pressed or otherwiseprocessed to remove the solvent, and the resulting composite solid isformed into the desired shape for implantation. Other additives may beincluded, e.g., antibiotics, prosthesis devices, radio-opacifyingagents.

The delivery compositions of U.S. Pat. No. 4,563,489 have relativelysmall masses and are used in relatively thin layers (i.e., in the rangeof 1 mm to 2 mm in thickness). In one example, implants are described asbeing shaped by pressing the wet BMP-PL precipitate in a mold to expressthe second solvent prior to drying. Wet (precipitated) composite wasalso shaped using glass molds to produce flakes, rods, films or plates.The patent also mentions that in preferred embodiments theBMP/biodegradable polymer delivery composition is formed into a dough,rod, film, flake or otherwise shaped as desired. The patent furthermentions that the BMP/PL composition, while still dispersed or dissolvedin solvent, may be formed into small pellets, flakes, platelets, etc.,by casting in molds and allowed to dry or harden.

Several other processing techniques have been utilized for production ofresorbable implants from the synthetic alpha-polyesters, such as PLA.U.S. Pat. No. 4,776,329 discloses the production of a resorbablecompressing screw for use in orthopaedic surgery by injection molding.U.S. Pat. No. 4,781,183 discloses the production of surgical structuralelements, such as plates or pins, consisting of bioabsorbable orsemi-bioabsorbable composites. Specifically, a bone fixation device isdisclosed based on an absorbable homopolymer of L-lactide or DL-lactideor a copolymer of L-lactide and a reinforcement material. Poly(L-lactide) was selected as the preferred matrix material. Thereinforcement is described to be either particulate, such ashydroxyapatite or tricalcium phosphate, or fibrous, such as alumina,polyethylene terephthalate, or ultra-high modulus polyethylene.

Composite materials used for production of bone fixation devices may bemanufactured by various routes. For particulate-filled systems, filleris typically added in the desired concentration to the bulk meltedpolymers in a stirred reactor vessel just subsequent to polymerization.Alternatively, particulate filler, such as tricalcium phosphate, may bethoroughly mixed with the melted bioabsorbable polymer under nitrogen orvacuum.

For fiber reinforced materials, solution impregnation and lamination ormelt impregnation and lamination techniques are typically utilized. Inthe former case, fibers or woven fabric may be immersed in a solution ofthe biodegradable polymer in methylene chloride. The impregnatedreinforcement may be dried, then laid up in a mold to a predeterminedthickness. Vacuum may be applied using a vacuum bag, then heat andcompression applied to consolidate the laminate.

Melt impregnation and lamination first typically require the making offilms of the biodegradable polymer by solvent casting or meltprocessing, or the preparation of fibrous mats by running a solution ofthe polymer into a non-solvent in a thin stream to form a stringyprecipitate. This precipitate may be pressed into a mat at roomtemperature. The films or mats may then be laid between yarn or fabriclayers in a mold of predetermined thickness and consolidated as above.

Poly(L-lactide)/alumina fiber laminates may be produced by laying upmelt-pressed poly(L-lactide) sheets and alumina fiber fabric in a moldand consolidating under heat and pressure. Poly(L-lactide)-Kevlarlaminates may be made by solution impregnation and lamination. Alaminate may also be formed by impregnating 1/2 " chopped alumina fiberwith poly(L-lactide) by stirring the chopped fiber in a chloroformsolution of the polymer, then drying and consolidating the mixture, byhot pressing in a mold, to give a laminate containing 30% alumina byvolume.

U.S. Pat. No. 4,550,449 discloses the production methods of directmachining of a high molecular weight, solid L(-) lactide polymer afterremoval from the reaction vessel and grinding and molding the polymer toform the desired implantable fixation device.

U.S. Pat. No. 4,645,503 discloses production of a moldable bone implantmaterial containing approximately 65-95% hard filler particles and abinder composed of approximately 35-5% of a biocompatible, biodegradablethermoplastic polymer which has fluidic flow properties at a selectedtemperature at or below about 60° C. Variation in biodegradation ratevia the usual routes for biodegradable polymers is described, namely,(1) adjustment of molecular weight, (2) substitution of the polymersub-unit (copolymerization), (3) blending with a slower degradingpolymer, or (4) increasing the surface area for hydrolysis by varyingthe proportion of binder and particles to provide voids or pores in thematerial.

It is an object of this invention to provide improved resorbablematerials and methods for making such materials which address at leastsome of the shortcomings of the prior art.

SUMMARY OF THE INVENTION

The present invention relates broadly to resorbable materials producedby the gelation of a solution of an independently-gelling singlepolylactide enantiomer.

The term "single polylactide enantiomer" is an abbreviated descriptionused herein to mean a homopolymer or copolymer of a single enantiomericlactide (i.e. either L-lactide or D-lactide). That is, the term means ahomopolymer or copolymer having substantially L-lactide or D-lactideenantiomeric monomer units in the polymer chain. Such polymers may beprepared by polymerization of a single enantiomeric lactide (i.e. eitherL-lactide or D-lactide). The term does not include blends ofpoly(D-lactide) with poly(L-lactide), nor does it include copolymers ofD- and L- lactide.

The term "independently-gelling" means that the single polylactideenantiomer is capable of gelling independently of any other additions tothe polymer solution. It should be understood that other materials maybe added to the solution to vary certain properties (such as resorptionrate or density) of the resorbable material product, but such additionsare not necessary in the practice of this invention to effect gelation.

In a first broad embodiment, the present invention provides a method formaking a resorbable material, comprising dissolving a single polylactideenantiomer in a solvent, such that the polymer solution is capable ofgelling independently of any other additions to the solution. Thepolymer solution is allowed to form a gel, and the gel is dried to formthe resorbable material product.

In a second broad embodiment, after the polymer solution forms a gel asdescribed above, the solvent may be replaced/extracted with anonsolvent, such that the polymer precipitates to form a substantiallymicroporous material. The microporous material is then dried to form theproduct.

In a third broad embodiment, the drying step may comprise firstpartially drying the gel or microporous material, followed by extractionof the organic solvent or nonsolvent molecules with water, then completedrying.

In the second broad embodiment discussed above, the nonsolvent may beorganic or it may be water. If it is organic, it may be desirable insome applications of this invention to immerse the microporous materialin water before the drying step, to extract the organic nonsolventmolecules.

If desired, the polymer solution may be cast in a mold prior to the gelforming step, and the gel may be removed from the mold after the gelforming step, such that the gel substantially retains the shape of themold. In this way, resorbable materials may be formed in desired shapeswithout the necessity of machine shaping.

Preferred solvents include acetone and ethyl acetate.

Preferably, the polymer is dissolved in the solvent to a concentrationof from about 1 to about 10% weight/volume (w/v). More preferably, theconcentration range is from about 2.5 to about 10% (w/v); mostpreferably, it is from about 7 to about 9% (w/v).

The preferred polymer is the homopolymer, poly(L-lactide). However, thepolymer may alternatively be a copolymer of either L-lactide orD-lactide and another alpha-hydroxy acid, such as glycolide, providedthat the copolymer is capable of independently gelling in solution.

In a preferred embodiment, the weight average molecular weight of thepolymer is between about 50,000 and 200,000, most preferably around100,000.

In order to alter the resorption rate or other characteristics of theproduct, a second material (e.g. another polymer) may be dissolved inthe solvent before the gel forming step. To obtain satisfactory gelling,the ratio of the single polylactide enantiomer to the second materialshould be at least about 1:9, with the addition preferably being made toa solution having a concentration of at least about 2.5% (w/v) of theenantiomeric lactide polymer. Depending upon the desired properties ofthe final product, the second material can be selected from numerouspossibilities, such as lactides, polymers of alpha-hydroxy acids,polymers of lactones, copolymers of at least one alpha-hydroxy acid,polyethylene oxides, polyurethane or copolymers containing athermoplastic elastomer (e.g. polyether or polyester).

Alternatively or in addition, a filler material may be added to thesolvent before the gel forming step.

The methods described above can be used to make resorbable materialswhich are much thicker than many prior art techniques based on solutionprocessing. Resorbable materials as used in this invention can be moldedto have virtually any minimum thickness desired. Thus, implant devicescan be made having thickness designed for the particular application.For example, in some cases an implant having minimum thickness aboveabout 2 mm may be desired; in other situations, thicker devices may beneeded, e.g. above about 5 mm or 10 mm minimum thickness.

Other embodiments of the invention include resorbable materials preparedby the methods described above, and use of such materials asimplantation devices, such as bone graft substitutes, bone fixationdevices, coatings for implants, or devices for controlled release ofbioactive materials. When used to form a bone graft substitute, theresorbable material may be machined with bores to achieve a honeycombstructure, facilitating bone growth through the device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a honeycomb bone graft substitute madeof a resorbable material provided by this invention.

FIG. 2 is a plan view of the bone graft substitute of FIG. 1.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

One preferred embodiment of the invention relates to a gel castingtechnique for resorbable synthetic alpha-polyesters, which may be usedfor producing novel bone repair materials or bone substitutes,resorbable medical implants and timed release carriers for medication.Formation of a distinct gel phase in the techniques of this inventionenables production of relatively thick-section, solid moldings.

In a preferred embodiment, gel production occurs from a solution ofpoly(L-lactide). The polymer is selected/designed such that it iscapable of gelling independently of any other polymer addition to thesolution.

The gel may be used as a medium to incorporate non-gelling or weaklygelling polymers (such as low molecular weight species, non-lactidepolymers, or lactide copolymers), in the material composition forcontrol of properties such as resorption rate and density, mechanicalproperties, shrinkage, and thermal characteristics. Gel casting can beused to vary morphology (e.g. solid versus microporous materials) and toproduce blends of homopolymers, copolymers and particulate fillers, suchas tricalcium phosphate. Control of material biodegradation rate byvariation of polymer type, molecular weight range, crystallinity andmorphology may therefore be facilitated.

Other embodiments of the invention include processes for preparing gelsfrom the gelling polymer and from blends of such polymer with resorbableand nonresorbable homopolymers, copolymers, and filler materials;processes for obtaining thick-section solid and microporousmaterials/foams from the gels; methods for controlling the shrinkage ofmicroporous materials containing a substantial amorphous component bycontrolled drying and extraction of plasticizing molecules; andresorbable implants in the form of honeycomb structures for repair oflong bones, being manufactured from microporous gel cast materials.

Gel casting could be extended to production of long lengths ofbiodegradable rod or bar by continuous casting methods, as practiced inthe metalworking industries. The gel could conceivably be extruded toform filaments or fibers, avoiding a precipitation stage in the case ofwet (or solution spinning) and elevated temperatures in the case of meltspinning.

It is generally known that resorbable alpha-polyester (e.g. lactide orglycolide) homopolymers or copolymers of differing molecular weight, andcopolymers of differing molar ratio and sequence length, exhibitmarkedly different resorption rates and mechanical and thermal behavior.The gel casting technique of the present invention can provide a methodfor tailoring resorption rates to meet specific end use requirements intissue repair or drug delivery.

In a preferred embodiment, the gelling medium is poly(L-lactide)(abbreviated hereinafter sometimes as "L-PLA") having an averagemolecular weight of around 100,000, which is sold commercially byPolysciences, Inc.

While L-PLA homopolymer is the preferred gelling medium, it should beappreciated that poly(D-lactide) homopolymer may be used. Furthermore,certain copolymers based on a single enantiomeric lactide, such aspoly(L-lactide co-glycolide) can function as the gelling medium,provided that the copolymer is designed to be capable of independentlygelling in solution.

Without wishing to be bound by theory, it appears that particular chainlengths or chain length distributions of the polymer facilitateproduction of a gel suitable for use in this invention. Specifically,the chain length distribution and structural regularity should allow theformation of effective gel junctions by crystallization and chainentanglements. Thus, if a copolymer is used as the gelling medium, itshould be structured such that the L-lactide (or D-lactide) sequenceshave sufficient length and regularity to permit formation of stable geljunctions or network points by crystallization and by the production ofeffective chain entanglements. Gel junctions or network points shouldconfer adequate gel strength for stability in the solvent swollen formand resist those forces generated by chain recoiling during the processof gel drying and shrinkage to the solid form, without destruction ofthe junction points.

The solvent may be acetone or ethyl acetate. Acetone is preferred sincepolymer dissolution is generally easier in this solvent.

Dissolution of a potential gel-forming polylactide polymer in acetoneappears to be highly dependent on the physical form of the startingmaterial. The 100,000 molecular weight poly(L-lactide) obtained fromPolysciences, Inc. (Batch No. 61490) was supplied in a fine, stringy orfibrous precipitate form and dissolved readily in acetone at 52° C.Poly(L-lactide) polymer obtained from Dupont [Batch No. 59010 L051,weight average molecular weight (M_(w))˜100,000] was supplied in theform of solid platelets or pellets (approximately 4×15×1 mm), which werepresumably produced by melt extrusion. Dissolution of the pellets wasnot achieved in acetone (0.4 gm in 10 cc solvent) at 52° C. in one hourand they retained their starting form without coalescing. In contrast,the Dupont material in precipitate form dissolved readily in acetone at52° C. to produce a 4% (w/v) solution. Gelation occurred on standing atroom temperature in less than 15 minutes. The poly(L-lactide)precipitate can be prepared, for example, by dissolution of 2 gm ofpolymer in 20 cc methylene chloride at room temperature, followed byprecipitation in 40 cc methanol which is agitated by a stirrer bar. Theprecipitate is dried at room temperature before use.

Dissolution of the above-mentioned Dupont poly(L-lactide) in acetone wasalso facilitated by using the film form of the polymer. As-receivedpellets were converted to a film by casting a 10% (w/v) solution of hepolymer in methylene chloride on a glass surface, followed by drying.

It is expected that a decrease in crystallinity of the startingpolylactide will also facilitate its dissolution in acetone and increaseits potential for use as a gel-forming medium.

Useful polymers and copolymers for blending with the gelling mediuminclude lactide homopolymers, non-lactide polymers such as poly epsiloncaprolactone, lactide copolymers, copolymers produced from mixtures oflactide and non-lactide comonomers such as lactones (e.g. epsiloncaprolactone) or other hydroxy acids (e.g. glycolic acid), lactides,non-lactide polymers (e.g. polyethylene oxide), or copolymers containing"soft blocks" of polyether, polyester or other similar polymers. Suchblending may enable variation of molecular weight distribution, density,shrinkage, and mechanical and thermal characteristics.

Useful fillers include particulates of bioceramics such as tricalciumphosphate and hydroxyapatite; non-resorbable discontinuous fibers ofalumina, carbon or polyethylene terephthalate; or resorbablediscontinuous fibers such as polyglycolic acid or calcium metaphosphate.

In a preferred embodiment of this invention, a method is provided forpreparing solid resorbable materials, comprising the steps of:

(1) polymer dissolution in a solvent;

(2) casting the solution in a mold;

(3) gel formation in situ;

(4) removal of the shaped gel from the mold; and

(5) drying to obtain solid material in relatively thick sections.

Solid materials may alternatively be produced by extracting the solventwith a nonsolvent (e.g. methanol) over around 24 hours before drying,then drying the material. Shrinkage may result in material consolidationto form a solid core encased in a layer of microporous material. Thislatter material may be removed by machining if desired.

For highly crystalline polymers, e.g. polylactide, the gel castingmethod described above may be altered to produce microporous materials(or foams) of good structural integrity and foam consistency byfollowing the steps (1)-(4) above, then converting the gel to amicroporous material by precipitation in a nonsolvent such as methanol,followed by drying.

The density of microporous blends containing certain amorphous polymerscan be controlled by predrying and water immersion subsequent to gelproduction. Extraction of solvent may remove the plasticizing effect oforganic molecules, thereby restricting chain recoiling of the amorphousphase, which may result in material shrinkage on drying.

If substantially amorphous polymers or semicrystalline polymers areincluded with the basic gelling polymer, the product gel may beconverted to a microporous material by precipitation in an organicnonsolvent, and/or immersion in water to remove the plasticizing effectof organic molecules, followed by drying. Also, the extent of shrinkageand, therefore, density of microporous materials containing asubstantial proportion (e.g. >about 25%) of amorphous polymer can becontrolled by partially drying the gel (or the methanol-treated gel) toa desired level and extracting/replacing the solvent or nonsolvent withwater prior to drying. This may remove the plasticizing effect of theorganic solvent or nonsolvent molecules, which may facilitate chainrecoiling in the amorphous phase, resulting in excessive shrinkage ofthe material on drying.

The resorption rate of biodegradable polymers may be influenced by thematerial form. Porosity generally facilitates fluid ingress throughoutthe material, exposing a large surface area of the material to chainscission by hydrolysis. Increased degradation rates can be expected.Porous implant surfaces could present a favorable surface for cellattachment and growth, enhancing its function as a biodegradablescaffold for tissue repair or implant fixation.

The release rate of medication from resorbable, polymeric deliverysystems may also be influenced by the porous character and density ofthe delivery vehicle. The control of density and, therefore, pore sizeand structure in resorbable polymers may be achieved by theabove-described drying/water treatment stage in the process ofmanufacture of microporous materials from blends containing an amorphouspolymeric component.

The resulting solid or microporous materials can be used to formimplantable devices of various shapes, e.g. a disc for nonunionfractures or a cylinder for repair of segmental defects. The advantagesof a microporous material include the increase in surface area forhydrolysis or breakdown of the implant and the presence of a potentiallybetter surface for attachment of osteoprogenitor cells.

As illustrated in FIGS. 1 and 2, the material can be machined to producea bone graft substitute 20 of macroporous character, for example bydrilling 100-500 μm bores 22 running the length of the implant andintersecting with the implant end surfaces 24. In a preferredembodiment, the macropores are about 500 μm in diameter, based on a holecenter spacing of 1 mm. In repair of long bones, the macropores mayallow marrow migration throughout the implant to establish a supply ofosetoprogenitor cells and growth factor and allow primary bone growthalong the pore channels. Gradual resorption of the implant bridge mayallow secondary bone formations to be established and bone remodeling totake place by load transfer to the ingrown tissue. A polymer blend ofslow resorbing polymer (L-PLA) and fast resorbing polymer [e.g.poly(DL-lactide co-glycolide)] can be used to produce an "enduringscaffold" system which provides a support element for immature boneformations during and after resorption of the fast degrading phase topromote and encourage satisfactory tissue repair, stability andremodeling.

EXMPLES

The following examples are designed to illustrate certain aspects of thepresent invention. The examples are not intended to be comprehensive ofall features and all embodiments of the present invention, and shouldnot be construed as limiting the claims presented herein.

Material shrinkage was measured with respect to the diameter of the gelon demold. Material density was estimated from measurements of thedimensions of a disc of material and its corresponding weight in air.Drying of materials was carried out in air under ambient conditionsunless otherwise specified. Polymer dissolution was aided by stirringwith a magnetic stirrer bar and, unless otherwise specified, the moldwas a 10 cc plastic syringe body.

EXAMPLE 1

A single component gel was produced by heating finely divided L-PLA(Polysciences, Inc., Mw 100,000, Batch No. 61490) in acetone at aconcentration of 7-9% (w/v), with agitation at a temperature of 46°-52°C., until dissolved (approximately 15 minutes). 7% (w/v) gave the bestresults.

The clear solution was poured into a mold and allowed to cool to roomtemperature under quiescent conditions. The cloud point, or the point atwhich opacity developed in solution due to crystal formation, wasaccompanied by a marked increase in solution viscosity, and occurred atapproximately 28°-32° C. for a 10% (w/v) solution. A weak gel was formedat 25° C., which was easily disrupted by stirring. The product gel whichformed in situ in the mold had a distinct white color and hardened overtime. It was firm enough to withstand demold after 30 minutes at roomtemperature (22°-24° C.). At that point, the demolded gel was allowed todry to remove the solvent and produce solid material. A shrinkage indiameter of approximately 50% relative to the demolded gel occurredafter 24 hours air drying.

EXAMPLE 2

A demolded gel prepared as in Example 1 was immersed in methanol toextract solvent and produce a microporous material on subsequent drying.

An acetone-based gel produced from a 7% (w/v) solution was immersed inmethanol for three days (50 cc methanol in 100 cc beaker with a changeof immersion medium at 24 hours). The methanol was allowed to evaporateand the material allowed to dry in the beaker over four days at roomtemperature. A shrinkage of approximately 40% occurred relative to thegel on demold and a density of 0.36 gm/cm³ was obtained for the productfoam/microporous material. Treatment of the demolded gel in methanol forthree days, followed by water immersion for three days, with a change inimmersion medium after 24 hours, slightly reduced the shrinkage to 37%and yielded a microporous material density of 0.33 gm/cm³ after dryingfor four days at room temperature.

An acetone-based gel of the preferred L-PLA polymer produced from a 7%(w/v) solution was redissolved by heating in an excess of solvent (e.g.1.1 gm gel in 10 cc acetone) at 50° C. in less than ten minutes.

EXAMPLE 3

A 2.5% (w/v) solution of L-PLA (Mw 100,000) in acetone was produced bydissolving 0.5 gm of the polymer in 20 cc of solvent at 50° C. Thesolution was poured into molds. On standing at room temperature, opacitydeveloped in solution after 45 minutes, denoting crystal formation. Ondemold after 19 hours, a strong, white gel was evident, which exhibiteda 65% shrinkage in diameter after five hours air drying at roomtemperature.

EXAMPLE 4

L-PLA of molecular weight 200,000 (Polysciences, Inc.), when heated inacetone at 50° C. at a concentration of 2 gm polymer to 20 cc ofsolvent, did not dissolve completely. Instead, a milky suspension ofpowder in solvent was obtained. A weak gel was, however, formed fromthis suspension after one hour at room temperature, presumably due todissolution of a certain fraction of the starting polymer. This samepolymer dissolved readily in p-dioxane to give a 10% (w/v) solution, butdid not gel under quiescent conditions at room temperature. L-PLA, witha weight average molecular weight of 50,000 (Polysciences, Inc.) whenheated in acetone at a 9% (w/v) concentration also resulted inincomplete dissolution (milkiness persisted). After standing at roomtemperature for 17 hours, a very weak, easily damaged gel was evident ondemold which collapsed under its own weight. Doubling the concentrationof 50,000 L-PLA in acetone also produced a weak gel on standing whichcracked or crumbled on drying.

EXAMPLE 5

The preferred polymer for the gelling medium (L-PLA, Mw 100,000)exhibited a crystalline melting point at approximately 160° C. Rapidcooling in the molten state from 230° C. resulted in increasingamorphous content, evidenced by the absence of a recrystallizingtransition on cooling. On reheating, no recrystallization of theamorphous component occurred.

In contrast, a weakly gelling lactide polymer (Mw 50,000), which wassubstantially unsuitable for use, exhibited a recrystallizing transitionat around 125° C., followed by a crystalline melting transition at 170°C. on reheating the amorphous form produced by rapid cooling. Thisreflected a greater chain mobility for this polymer.

These tests suggest that operable semi-crystalline polymers suitable forproducing the gelling medium in the disclosed gel casting technique maybe characterized by a limited chain mobility due to molecular weightdistribution, which impedes recrystallization of the amorphous form ofthe polymer on heating.

EXAMPLE 6

Formation of a distinct gel phase immediately following polymerdissolution tends to enable production of thick solid moldings.

An 11 mm diameter cylinder of the preferred L-PLA was produced by airdrying for 17 hours a gel produced from a 9% (w/v) solution in acetone,followed by annealing for 56 hours at 72° C. Final shrinkage (diameter)was 62%. In contrast, the absence of gelation in a 7% (w/v) solution ofthe preferred L-PLA polymer in chloroform at room temperature resultedin the formation of a film or coating on the mold walls on solventevaporation over four days.

Shrinkage forces developed during drying of the gel at room temperatureyielded a homogenous, thick-section solid product with a state ofconsolidation visually similar to that of a thermoplastic processed inthe melt at high temperatures and pressures by injection molding orextrusion. Material consolidation in gel casting was achieved in a"cold" system through a combination of factors. The gel's liquid mediumprovided crystal mobility and chain flexibility in the amorphous phaseby a plasticizing effect. This, coupled with the forces generated by thetendency of macromolecules in the solvent-swollen, amorphous phase torecoil on evaporation of the swelling medium, resulted in the observedgood material consistency.

EXAMPLE 7

An 11% (w/v) solution of low molecular weight L-PLA (Mw 2000,Polysciences, Inc.) was produced by dissolving 2.2 gm polymer in 20 ccacetone at 52° C. and allowed to stand at room temperature for 21 hours.An extremely weak gel was evident on demold, which did not retain themolded form but collapsed under its own weight, eventually drying to aweak, brittle solid.

12% (w/v) solutions in acetone of poly(DL-lactic acid) [Mw 20,000,Polysciences, Inc.] or 70:30 poly(DL-lactide co-glycolide) copolymer [Mw30-60,000, Polysciences, Inc.]or 90:10 poly(DL-lactide co-glycolide)copolymer [Mw 30-60,000, Polysciences, Inc.] or 85:15 poly(DL-lactideco-glycolide) copolymer [Mw 40-100,000, Dupont] did not gel on standingat room temperature. Gradual evaporation of solvent occurred from thebulk solution, resulting in formation of a viscous fluid.

These polymers were combined with the preferred gelling L-PLA polymer,for example, in the ratio 25 (L-PLA):75 (other), by simultaneousdissolution in acetone to produce a blended polymer gel. The gel wassubsequently converted to a solid material by drying/solvent extraction.For predominantly crystalline polymer additions, e.g. lower molecularweight L-PLA, the gel was converted to a microporous material byprecipitation in a nonsolvent, followed by drying. For substantiallyamorphous polymer additions to the basic gelling polymer, the gel wasconverted to a microporous material by precipitation in a nonsolventand/or immersion in water (to remove the plasticizing effect of organicmolecules), followed by drying. Non-gelling or weakly gelling polymerswere incorporated into a particular material composition by using L-PLAas the gelling medium.

EXAMPLE 8

A 30% solid, particulate-filled, resorbable material consisting oftricalcium phosphate in L-PLA was produced by dissolving 1.4 gm L-PLA(Mw 100,000) in 20 cc acetone at 52° C. On dissolution of the polymer(in approximately 15 minutes), 0.6 gm of tricalcium phosphate (TCP) [J.T. Baker]was added, with stirring until a uniform dispersion wasobtained. The suspension was poured into a mold and allowed to stand atroom temperature. A strong, firm gel was obtained on demold after 11/2hours, which exhibited a shrinkage value of 55% over 29 hours air dryingto yield a solid, particulate-filled material having a density of 1.02gm/cm³.

An acetone-based gel of TCP-filled, L-PLA, produced as described above,was immersed in methanol on demold for five days, then air dried forfour days. The microporous material obtained exhibited a shrinkage of26% and a density of 0.27 gm/cm³.

EXAMPLE 9

A 29% TCP particulate-filled microporous blend of L-PLA with 70:30poly(DL-lactide co-glycolide) copolymer [Mw 30-60,000, Polysciences,Inc.] was produced by dissolving 0.8 gm and 2.4 gm of each polymer,respectively, in 20 cc acetone at 52° C. Particulate filler (1.28 gm)was dispersed in the solution by stirring. The suspension wastransferred to molds and allowed to stand at room temperature for 22hours before demold, whereupon a weak, sticky gel was obtained.(Sedimentation of TCP filler was limited prior to gel formation by theviscosity of the blended polymer solution.) The gel was subsequentlyimmersed in 50 cc methanol in a 100 cc beaker for two days with asolvent change at 24 hours. The nonsolvent was then allowed to evaporateand the material allowed to dry in the beaker over three days. The TCPparticulate-filled L-PLA:PLG microporous blend obtained exhibited ashrinkage of 28% and a density of 0.6 gm/cm³.

EXAMPLE 10

Solid L-PLA material (Mw 100,000, Polysciences, Inc.) was produced bydissolving 1.8 gm of this preferred gelling polymer in 20 cc acetone at52° C. The solution was transferred to cylindrical molds and allowed tostand at room temperature. The gel obtained on demold after 39 minuteswas air dried under ambient conditions to consolidate the polymer as asolid rod. Thermal transitions were determined by Differential ScanningCalorimetry (DSC). On heating at 20° C./min., from 10° C. to 30° C., asingle melting peak was observed at 159° C. No recrystallization peakwas evident on immediate cooling of the sample at 50° C./min. to 10° C.Reheating the sample at 50° C./min to 230° C. revealed only a glasstransition (Tg) at 70° C., indicating that the polymer exists mainly inthe amorphous phase after rapid cooling from the melt.

EXAMPLE 11

A 50:50 blend of L-PLA (Mw 100,000) and poly(DL-lactide) [Mw 20,000,Polysciences, Inc.] was produced by codissolving 1 gm of each polymer in20 cc acetone at 52° C. The solution was poured into cylindrical plasticmolds and allowed to stand at room temperature. The product blended gelwas demolded after 55 minutes and air dried to consolidate the materialas a solid rod. Thermal transitions were revealed by DSC, using the testprocedure described in Example 10. A broad, spiky melting peak wasobserved on heating, extending from 120°-160° C. and centered around140° C. No recrystallization peak was evident on cooling the sample. Aglass transition was observed on remelting at 53° C.

The (DL-lactide) polymer showed a glass transition at 35° C. on heating,which shifted to 45° C. after cooling from 230° C. and reheating.

EXAMPLE 12

A 25:75 blended solution of high molecular weight L-PLA (Mw 100,000) andlow molecular weight L-PLA (Mw 2,000, Polysciences, Inc.) was producedby dissolving 0.6 gm and 1.8 gm of each polymer, respectively, in 20 ccacetone at 50° C. The solution was transferred to molds and allowed tostand at room temperature. The resultant firm gel was demolded in 30minutes, following a rapid cloud point of five minutes. Air drying thegel over five days resulted in a shrinkage of 44% and production of ahard, waxy solid. A 25:75 blended gel of high and low molecular weightL-PLA, demolded after 19 hours, was immersed in 50 cc methanol in a 100cc beaker for two days with a change of medium after 24 hours. Themethanol was allowed to evaporate and the material allowed to dry in thebeaker over four days at room temperature. The blended, microporousmaterial obtained exhibited a shrinkage of 19% and a density of 0.29 to0.43 gm/cm³.

The thermal testing procedure described in Example 10 revealed meltingpeaks at 136° C. and 155° C. for 25:75 microporous material, roughlycorresponding to the individual homopolymer components, and norecrystallizing transition on cooling. On reheating, a glass transitionwas observed at 63° C., a broad recrystallizing transition at 130° C.and a melting peak at 155° C. Solid, low molecular weight L-PLA obtainedby air drying the weak gel produced from an 11% (w/v) solution inacetone revealed low broad melting peaks centered around 104° C. and118° .C and the main melting peak at 140° C. No recrystallizationtransition was observed on cooling. On reheating, a glass transition wasevident at 50° C. and a small melting peak at 143° C.

The lower molecular weight polymer species introduced into the blendallowed sufficient chain mobility for recrystallization to occur fromthe amorphous form on heating. Recrystallization did not occur for theamorphous form of the single higher molecular weight polymer.

It may be possible to vary the crystallinity of a blend by isothermalconditioning.

EXAMPLE 13

A 25:75 blended solution of L-PLA and a 70:30 poly(DL-lactideco-glycolide) copolymer [Mw 30-60,000, Polysciences, Inc.] was producedby co-dissolution of 0.6 and 1.8 gm of each polymer, respectively, in 20cc of acetone at 52° C. The solution was transferred to molds andallowed to stand at room temperature. An acetone seal was applied to thegel after one hour to prevent surface drying at long demold times. Theblended gel produced on demold after 21 hours was subsequently immersedin methanol for four days, 18 hours before drying at room temperaturefor one week. Shrinkage of the methanol-based material occurred ondrying to the extent of 48%, to yield a practically solid polymer core.An acetone-based gel was immersed in methanol for five days, 18 hours,then immersed in water for 21 hours prior to drying. In this case, themioroporous blend obtained exhibited a shrinkage of only 13% and adensity of 0.25 gm/cm³.

The density of microporous materials could be varied by water treatmentsubsequent to acetone extraction in methanol. Extraction of organicliquid from the material and its substitution by water removed theplasticizing effect of the organic molecules, raised the Tg and therebyrestricted chain recoiling of the amorphous phase, which resulted inmaterial shrinkage on drying.

25:75 acetone-based gels of L-PLA and 70:30 poly(DL-lactideco-glycolide) were demolded after 24 hours and immersed in methanol (50cc methanol in 100 cc beaker) for three days, with a change of immersionmedium at 24 hours. Samples were then air dried for time periods of 0,60 and 80 minutes before immersion in water for three days, with achange in immersion medium at 24 hours. Samples were finally air driedunder ambient conditions for three days to give uniformly microporousmaterials with the final shrinkage and density values shown in Table 1.

                  TABLE 1                                                         ______________________________________                                        Air drying time (minutes)                                                                      0          60     80                                         prior to water immersion                                                      Final foam shrinkage (%)                                                                       5          15     19                                         Foam density (gm/cm.sup.3)                                                                     0.19       0.22   0.29                                       ______________________________________                                    

EXAMPLE 14

A 25:75 blended solution of L-PLA and 85:15 poly(DL-lactic co-glycolide)[Mw 40-100,000, Dupont] was produced by dissolution of 0.8 gm and 2.4 gmof each polymer, respectively, in 20 cc acetone at 52° C. The solutionwas transferred to molds and allowed to stand at room temperature. Acloud point was observed after approximately 15 minutes. On demold after24 hours, gel samples were air dried for time periods of 0, 15, 45, and75 minutes before immersion in water for three days, with a change ofimmersion medium after 48 hours. Drying of the microporous materialsresulted in the final shrinkage and density values shown in Table 2,with foam properties ranging from tough and pliable to hard-yet-tough asdensity increased with predry time.

                  TABLE 2                                                         ______________________________________                                        Air drying time (minutes)                                                                      0        15     45     75                                    prior to water immersion                                                      Final foam shrinkage (%)                                                                       8        10     17     20                                    Foam density (gm/cm.sup.3)                                                                     0.22     0.25   0.32   0.38                                  ______________________________________                                    

EXAMPLE 15

Poly(DL-lactide) [Mw 40-100,000, Dupont] was dissolved in acetone toproduce a 12% (w/v) solution, transferred to a 10 cc syringe body andallowed to stand at room temperature. Gelation did not result andsolvent evaporation occurred over seven days, to leave a coating on themold walls. A 25:75 blended solution of L.PLA and poly(DL-lactide) wasproduced by co-dissolution of 0.8 gm and 2.4 gm of each polymer,respectively, in 20 cc acetone at 52° C. The solution was transferred tomolds and allowed to stand at room temperature. A cloud point wasobserved after approximately 10 minutes. An acetone seal was applied tothe gel after 30 minutes to prevent surface drying at long demold times.On demold after 21 hours, a soft gel was obtained, which was immersed inmethanol for three days with a change of immersion medium after 22hours. Immersion of the methanol-based material for three days in water,with a change in medium after 24 hours, prior to air drying resulted ina white, microporous material which exhibited a shrinkage of 1% and adensity of 0.18 gm/cm³.

On demold after 21 hours, an acetone-based gel sample was air dried for65 minutes before immersion in water for three days, with a change ofimmersion medium after 24 hours. Drying of the microporous material soobtained resulted in a final shrinkage of 26% and a density of 0.40gm/cm³.

L.PLA can be used as a gelling medium to incorporate non-gellingpolymers in a particular material composition for adjustment ofresorption rates, for example.

EXAMPLE 16

A 50:50 blended solution of L-PLA and low molecular weightpolycaprolactone (Mw 15,000, Polysciences, Inc.) was prepared byco-dissolution of 0.7 gm of each polymer in 10 cc acetone at 52° C. Thesolution was transferred to a mold and allowed to stand at roomtemperature. A cloud point was observed after 30 minutes. A firm, whitedamage-tolerant gel was obtained on demold after 25 hours, which wasimmersed in methanol for two days, 21 hours. Drying of thismethanol-based material at room temperature for two days, 19 hoursresulted in a shrinkage of 30% and a density of 0.45 gm/cm³ for theresulting firm, white, microporous material.

Treatment of the methanol-based material in a 50% methanol/water mixturefor two days, 19 hours, then water for six days prior to air drying forfour days resulted in a microporous material which exhibited a shrinkageof 15% relative to the demolded gel and a density of 0.26-0.29 gm/cm³.DSC revealed melting transitions at 64° C. and 160° C., corresponding tothe individual blend components.

EXAMPLE 17

A 50:50 blended solution of L-PLA (Mw 100,000 Polysciences, Inc.) andDL-lactide [Mw 144.12, Polysciences, Inc.) was prepared byco-dissolution of 0.7 gm of each material in acetone at 52° C. Thesolution was transferred to a cylindrical mold and allowed to stand atroom temperature. An acetone seal was applied after 30 minutes. A firm,white, damage-tolerant gel was obtained on demold after 24 hours, whichwas immersed in methanol for two days, 21 hours. Drying of thismethanol-based material for two days, 19 hours resulted in a hard, whitemicroporous material exhibiting a shrinkage of 37% relative to thedemolded gel and a density of 0.38 gm/cm³. Treatment of themethanol-based material for two days, 19 hours in a 50% methanol/watermixture, followed by immersion in water for six days, prior to airdrying (four days), resulted in a firm, white microporous material whichexhibited a shrinkage of 19% and a density of 0.16 gm/cm³. DSC revealeda small melting peak at 60° C. and the main melting transition at 160°C.

EXAMPLE 18

A bone repair device potentially suitable for general bone augmentationand reconstruction or for repairing large segmental defects and nonunionfractures was fabricated from a microporous 25:75 blend of L-PLA and85:15 poly(DL-lactide co-glycolide) produced by the disclosed gelcasting technique.

0.6 gm of L-PLA (Mw 100,000) and 1.8 gm of 85:15 poly(DL-lactideco-glycolide) copolymer (Medisorb, Mw 40-100,000, Dupont) were dissolvedwith stirring in 20 cc acetone at 52° C. in approximately 15 minutes.The solution was transferred to molds and allowed to stand at roomtemperature for 24 hours before demold. The gel obtained was dried inair for 45 minutes to give a shrinkage of 19%, then immersed in waterfor three days, with a change in immersion medium after 24 hours. Airdrying of the microporous material obtained over four days resulted in afinal shrinkage of 17% and a density of 0.32 gm/cm³. This stock materialwas machined further to produce a particular honeycomb design for repairof long bones.

The instant invention has been disclosed in connection with specificembodiments. However, it will be apparent to those skilled in the artthat variations from the illustrated embodiments may be undertakenwithout departing the spirit and scope of the invention.

What is claimed is:
 1. A method for making a resorbable implantationdevice, comprising the steps of:dissolving an independently-gellingsingle polylactide enantiomer in a solvent to form a polymer solution;casting the polymer solution in a mold; allowing the polymer solution tocool to form a gel capable of substantially retaining the shape of themold upon removal therefrom and handling thereof; and drying the gel toform a resorbable implantation device.
 2. A method for making aresorbable implantation deice, comprising the steps of:dissolving anindependently-gelling single polylactide enantiomer in a solvent to forma polymer solution; casting the polymer solution in a mold; allowing thepolymer solution to cool to form a gel capable of substantiallyretaining the shape of the mold upon removal therefrom and handlingthereof; extracting the solvent with a nonsolvent such that the polymerprecipitates to form a substantially microporous material; and dryingthe microporous material to form a resorbable implantation device. 3.The method of claim 2, wherein the nonsolvent is organic.
 4. The methodof claim 3, further comprising the step of, after the extracting stepand before the drying step, immersing the microporous material in waterto extract the organic nonsolvent molecules.
 5. The method of claim 2,wherein the nonsolvent is water.
 6. The method of claim 1 or 2, whereinthe solvent is acetone or ethyl acetate.
 7. The method of claim 1 or 2,wherein the independently-gelling single polylactide enantiomer isdissolved in the solvent to a concentration of from about 1 to about 10%weight/volume.
 8. The method of claim 1 or 2, wherein theindependently-gelling single polylactide enantiomer is dissolved in thesolvent to a concentration of from about 2.5 to about 10% weight/volume.9. The method of claim 1 or 2, wherein the independently-gelling singlepolylactide enantiomer is dissolved in the solvent to a concentration offrom about 7 to about 9% weight/volume.
 10. The method of claim 1 or 2,wherein the independently-gelling single polylactide enantiomer is basedon L-lactide.
 11. The method of claim 1 or 2, wherein theindependently-gelling single polylactide enantiomer is poly L-lactide).12. The method of claim 1 or 2, wherein the independently-gelling singlepolylactide enantiomer is based on D-lactide.
 13. The method of claim 1or 2, wherein the independently-gelling single polylactide enantiomer ispoly(D-lactide).
 14. The method of claim 1 or 2, wherein theindependently-gelling single polylactide enantiomer is a copolymer oflactide and another alpha-hydroxy acid.
 15. The method of claim 14,wherein the other alpha-hydroxy acid comprises glycolic acid.
 16. Themethod of claim 1 or 2, wherein the independently-gelling singlepolylactide enantiomer has a weight average molecular weight of betweenabout 50,000 and 200,000.
 17. The method of claim 1 or 2, wherein theindependently-gelling single polylactide enantiomer has a weight averagemolecular weight of around 100,000.
 18. The method of claim 1 or 2,wherein a second material is dissolved in the solvent before the gelforming step.
 19. The method of claim 18, wherein the ratio of theindependently-gelling single polylactide enantiomer to the secondmaterial is at least about 1:9.
 20. The method of claim 18, wherein thesecond material comprises a polymer.
 21. The method of claim 20, whereinthe second polymer comprises a polymer of an alpha-hydroxy acid, apolymer of a lactone, a copolymer at least one alpha-hydroxy acid, apolyethylene oxide, or a copolymer containing a thermoplastic elastomer.22. The method of claim 1 or 2, wherein a filler material is added tothe solvent before the gel forming step.
 23. The method of claim 1 or 2,wherein the molded gel has a minimum thickness of at least about 2 mm.24. The method of claim 1 or 2, wherein the molded gel has a minimumthickness of at least about 5 mm.
 25. The method of claim 1 or 2,wherein the molded gel has a minimum thickness of at least about 10 mm.26. The method of claim 1, wherein the drying step comprises:partiallydrying the gel; extracting the solvent molecules with water to form amicroporous material; and drying the water extracted microporousmaterial.
 27. The method of claim 2, wherein the drying stepcomprises:partially drying the microporous material; extracting thenonsolvent molecules with water; and drying the water extractedmicroporous material.
 28. A method for making a resorbable implantationdevice, comprising the steps of:heating an independently-gelling singlepolylactide enantiomer, having a weight average molecular weight ofbetween about 50,000 and 200,000, in acetone or ethyl acetate, such thatsaid enantiomer dissolves in the acetone or ethyl acetate to form apolymer solution; casting the polymer solution in a mold; allowing thepolymer solution to cool to form a gel capable of substantiallyretaining the shape of the mold upon removal therefrom and handlingthereof; and drying the gel to form a resorbable implantation device.29. A method for making a resorbable implantation device, comprising thesteps of:heating an independently-gelling single polylactide enantiomer,having a weight average molecular weight of between about 50,000 and200,000, in acetone or ethyl acetate, such that said enantiomerdissolves in the acetone or ethyl acetate to form a polymer solution;casting the polymer solution in a mold; allowing the polymer solution tocool to form a gel capable of substantially retaining the shape of themold upon removal therefrom and handling thereof; extracting the acetoneor ethyl acetate with a nonsolvent such that the polymer precipitates toform a substantially microporous material; and drying the microporousmaterial to form a resorbable implantation device.
 30. The method ofclaim 1 or 28, further comprising the step of forming at least one borein the gel.
 31. The method of claim 2 or 29, further comprising the stepof forming at least one bore in the microporous material.
 32. The methodof claim 1, 2, 28, or 29, further comprising the step of incorporating abioactive material into the resorbable implantation device.